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Gene Expression Patterns in Peripheral Blood Mononuclear Cells Associated with Asthma Exacerbation Attack

ABSTRACT: A large, prospective, non-interventional study was designed to study gene expression changes in peripheral blood mononuclear cells (PBMCs) associated with asthma exacerbations over the course of a year. PBMC samples were collected from subjects at the time of the study visits defined as 1) Quiet: during stable disease at 3 month intervals, 2) Exacerbation: during a 14 day period of deteriorating asthma and 3) Follow-up: within 14 days after cessation of an exacerbation. Gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared.

ORGANISM(S): Homo sapiens

PROVIDER: GSE19301 | GEO | 2011/07/14

SECONDARY ACCESSION(S): PRJNA120889

REPOSITORIES: GEO

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Gene Expression Patterns in Peripheral Blood Mononuclear Cells Associated with Asthma Exacerbation Attack

Project description:A large, prospective, non-interventional study was designed to study gene expression changes in peripheral blood mononuclear cells (PBMCs) associated with asthma exacerbations over the course of a year. PBMC samples were collected from subjects at the time of the study visits defined as 1) Quiet: during stable disease at 3 month intervals, 2) Exacerbation: during a 14 day period of deteriorating asthma and 3) Follow-up: within 14 days after cessation of an exacerbation. Gene expression levels during stable asthma, exacerbation, and two weeks after an exacerbation were compared. This series of samples comprises of peripheral blood mononuclear cells (PBMCs) collected during the following study visits (a) quiet (N=394 samples from 118 subjects), (b) exacerbation (N=166 samples from 118 subjects) and (c) follow-up (N=125 samples from 102 subjects)

2011-07-13 | E-GEOD-19301 | biostudies-arrayexpress

Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures.

Project description:Acute respiratory illness (ARI) is the leading cause of asthma exacerbations yet the mechanisms underlying this association remain unclear. To address the deficiencies in our understanding of the molecular mechanisms driving ARI-induced asthma exacerbations, we undertook a transcriptional profiling study of the nasal mucosa over the course of ARI amongst individuals with a history of asthma, allergic rhinitis and no underlying respiratory disease. We found that ARI is characterized by dynamic, time-specific transcriptional profiles whose magnitudes of expression are influenced by underlying respiratory disease and the mucosal repair signature evoked during ARI. Most strikingly, we report that asthmatics that experience ARI-induced exacerbations are characterized by a reduced but prolonged inflammatory immune response, inadequate activation of mucosal repair and the expression of a newly described exacerbation-specific signature. Findings from our study represent a significant contribution towards clarifying the complex molecular interactions which typify ARI-induced asthma exacerbations. Upon the onset of ‘common cold’, volunteers were instructed to attend the first of three required visits to the study clinic. The first and second visits were designed to obtain samples and clinical data during the early and late stages of symptomatic illness respectively, whereas the third visit would occur when volunteers were asymptomatic and serve as a prospective baseline (BL) for the study.

2013-08-02 | E-GEOD-46171 | biostudies-arrayexpress

Vastus lateralis muscle of patients with an acute COPD exacerbation

Project description:To further unravel the potential molecular mechanisms involved in the loss of muscle function during an acute exacerbation, a cross-sectional microarray study was designed to compare the gene expression profile of the vastus lateralis muscle in patients with an acute COPD exacerbation and in stable COPD patients. Keywords: cross-sectional patient study A cross-sectional microarray study was designed. The microarray screening was performed on a vastus lateralis biopsy obtained from 4 patients with an acute COPD exacerbation and 5 stable COPD patients. No replicates or dye-swaps were included.

2009-03-13 | E-GEOD-10828 | biostudies-arrayexpress

Proteome analysis of lung tissue from mice with allergic asthma, influenza-induced exacerbation of asthma (or treated with dexamethasone) vs. healthy mice

Project description:We have run shotgun proteomic analysis of lung proteome from mice with allergic asthma, influenza-induced exacerbation of asthma (or treated with dexamethasone) vs. healthy mice using LC-MS/MS. PRM proteomic analysis coupled with stable isotopic labelling was performed for quantification of protein STAT1. Protein digestion was done with Trypsin/Lys-C mix endoproteinase.

2021-10-01 | MSV000088182 | MassIVE

Vastus lateralis muscle of patients with an acute COPD exacerbation

2009-03-14 | GSE10828 | GEO

Inhibition of γ-glutamyl transpeptidase suppresses LPS induced asthma exacerbation in a mouse model

Project description:To investigate the role of γ-glutamyltranspeptidase in severe asthma, we established an OVA/ LPS-induced asthma model. Inflammation analysis and second-generation sequencing revealed the mechanism by which inhibition of γ-glutamyltranspeptidase inhibited LPS-induced asthma exacerbation in mice.

2023-07-05 | GSE217834 | GEO

Asthmatics with exacerbation during acute respiratory illness exhibit unique transcriptional signatures.

2013-08-02 | GSE46171 | GEO

Untargeted metabolomics on plasma from children with asthma, comparing exacerbation-prone to non-exacerbation-prone

Project description:Background: Some children with asthma remain poorly controlled and have recurrent exacerbations despite treatment with inhaled corticosteroids. Aside from prior exacerbations, there are currently no reliable predictors of exacerbation-prone asthma in these children and limited understanding of potential underlying mechanisms. Objective: We sought to quantify small molecules in the plasma of children with exacerbation- prone asthma through mass spectrometry-based metabolomics. We hypothesized that the plasma metabolome of these children would differ from that of children with non-exacerbation- prone asthma. Methods: Plasma metabolites were extracted from four pediatric asthma cohorts (n=215 total, n=41 with exacerbation-prone asthma) and detected using a ZIC-HILIC column coupled to a Q Exactive HF mass spectrometer. High-confidence annotations were retained for univariate analysis and were confirmed by a sensitivity analysis in subjects on high-dose inhaled corticosteroids. Metabolites that varied by cohort were excluded. Metaboanalyst was used to identify pathways of interest. Concentrations were calculated by reference standardization to NIST SRM 1950. Results: We identified 32 unique, cohort-independent metabolites that differed in children with exacerbation-prone asthma compared to children with non-exacerbation-prone asthma. Comparison of metabolite concentrations to literature-reported values for healthy children revealed that most metabolites were decreased in both asthma groups, but more so in exacerbation-prone asthma. Pathway analysis identified arginine, lysine, and methionine pathways as most impacted. Conclusions: Several plasma metabolites are perturbed in children with exacerbation-prone asthma and are largely related to arginine, lysine, and methionine pathways. While validation is needed, plasma metabolites may be potential biomarkers for exacerbation-prone asthma in children.

2022-07-25 | ST002251 | MetabolomicsWorkbench

Gene expression data from severe asthmatic children: PBMC profiles during acute exacerbation versus convalescence

Project description:Severe asthma exacerbations in children requiring hospitalisation are typically associated with viral infection, and occur almost exclusively amongst atopics, but the significance of these comorbidities is unknown. We hypothesised that underlying interactions between immunoinflammatory pathways related to responses to aeroallergen and virus are involved, and that evidence of these interactions is detectable in circulating cells during exacerbations. To address this hypothesis we used a genomics-based approach involving profiling of PBMC subpopulations collected during acute exacerbation versus convalescence by microarray and flow cytometry.

2009-05-09 | GSE16032 | GEO

Virograms for prediction of predisposition to asthma exacerbation

Project description:Background: Clinical transcriptomics of peripheral blood mononuclear cells (PBMC) are coming into focus as a surrogate approach for prognosis, diagnosis, biomarker discovery and examination disease mechanisms. However, bioassays paired with transcriptomic analytic tools are yet to be developed and made available at point of care. Harnessing personal dynamic genomic responses to tailor patient asthma treatment or prevent disease exacerbations remain unmet medical needs. Method: We developed a rhinovirus-stimulated peripheral blood based-assay (virogram assay) coupled with single-subject analytics (N-of-1-patwhays) to capture dynamic genome-wide expression and dysregulated pathways to retrospectively predict childhood asthma exacerbation. We hypothesized that some genomic factors might predispose any given individual, healthy or asthmatic, to a set of similar transcriptional responses to rhinovirus stimulation. We first generated a classifier from paired sample microarrays, control and stimulated PBMC from healthy subjects and applied this classifier on the transcriptomic analysis of control and HRV-stimulated PBMC samples (virogram assay) from children with asthma. Results: The analysis of the different genomic responses of single-subject paired PBMC samples (HRV-stimulated and control) derived from healthy individuals (external dataset) enabled the discovery of dysregulated pathways related to acquired immunity, epigenetics and morphogenesis. The classifier built on these results and applied on the transcriptional analysis derived from the virogram assay predicted that the risk of asthma exacerbation among asthmatic subjects with an accuracy of 70%. Conclusion: We provide evidence that clinical prognosis can be predicted with a PBMC based-bioassay aligned with adequate single-subject analytics to assess dynamic transcriptomic response to specific disease-associated stimuli.

2016-05-01 | GSE68479 | GEO

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